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Science 18 July 2008:
Vol. 321. no. 5887, pp. 367 - 369
DOI: 10.1126/science.1159746
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Perspective

Outwitting Multidrug Resistance to Antifungals

Brian C. Monk and Andre Goffeau*

The economic cost of fungal infection and its mortality associated with multidrug resistance remain unacceptably high. Recent understanding of the transcriptional regulation of plasma membrane efflux pumps of modest specificity provides new avenues for the development of broad-spectrum fungicides. Together with improved diagnosis and indirect intervention via inhibition of the energy supply for drug efflux, we envisage multifunctional azole analogs that inhibit not only ergosterol biosynthesis and drug efflux-pump activity but also activation of the transcriptional machinery that induces drug efflux-pump expression.

Department of Oral Sciences, Faculty of Dentistry, University of Otago, Post Office Box 647, Dunedin, New Zealand; and Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, 1348, Belgium.

* To whom correspondence should be addressed. E-mail: andre.goffeau{at}uclouvain.be

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Efflux-Mediated Antifungal Drug Resistance.
R. D. Cannon, E. Lamping, A. R. Holmes, K. Niimi, P. V. Baret, M. V. Keniya, K. Tanabe, M. Niimi, A. Goffeau, and B. C. Monk (2009)
Clin. Microbiol. Rev. 22, 291-321
   Abstract »    Full Text »    PDF »
Mutations Define Cross-talk between the N-terminal Nucleotide-binding Domain and Transmembrane Helix-2 of the Yeast Multidrug Transporter Pdr5: POSSIBLE CONSERVATION OF A SIGNALING INTERFACE FOR COUPLING ATP HYDROLYSIS TO DRUG TRANSPORT.
Z. E. Sauna, S. S. Bohn, R. Rutledge, M. P. Dougherty, S. Cronin, L. May, D. Xia, S. V. Ambudkar, and J. Golin (2008)
J. Biol. Chem. 283, 35010-35022
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)